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Fragment Screening Using X-Ray Crystallography

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Fragment-Based Drug Discovery and X-Ray Crystallography

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 317))

Abstract

The fragment-based approach is now well established as an important component of modern drug discovery. A key part in establishing its position as a viable technique has been the development of a range of biophysical methodologies with sufficient sensitivity to detect the binding of very weakly binding molecules. X-ray crystallography was one of the first techniques demonstrated to be capable of detecting such weak binding, but historically its potential for screening was under-appreciated and impractical due to its relatively low throughput. In this chapter we discuss the various benefits associated with fragment-screening by X-ray crystallography, and describe the technical developments we have implemented to allow its routine use in drug discovery. We emphasize how this approach has allowed a much greater exploitation of crystallography than has traditionally been the case within the pharmaceutical industry, with the rapid and timely provision of structural information having maximum impact on project direction.

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Acknowledgments

The authors gratefully acknowledge the support of many people at Astex Therapeutics who have contributed to aspects of the work presented here. We would also like to thank Dr Chris Murray and Dr Harren Jhoti for valuable suggestions regarding the content of this chapter.

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  1. Astex Therapeutics Ltd, 436 Cambridge Science Park, Milton Road, Cambridge, CB4 0QA, UK

    Thomas G. Davies & Ian J. Tickle

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  1. Thomas G. Davies
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Correspondence to Thomas G. Davies .

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  1. Astex Pharmaceuticals, Milton Road, Cambridge, CB4 0QA, United Kingdom

    Thomas G. Davies

  2. , Department of Biochemistry, University of Cambridge, Tennis Court Road 80, Cambridge, CB2 1GA, United Kingdom

    Marko Hyvönen

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Davies, T.G., Tickle, I.J. (2011). Fragment Screening Using X-Ray Crystallography. In: Davies, T., Hyvönen, M. (eds) Fragment-Based Drug Discovery and X-Ray Crystallography. Topics in Current Chemistry, vol 317. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2011_179

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